21-46111301-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001849.4(COL6A2):c.-27-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 587,398 control chromosomes in the GnomAD database, including 73,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (16835 hom., cov: 33)
  • Exomes 𝑓: 0.50 (56774 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.290

Genes affected

COL6A2 (HGNC:2212): (collagen type VI alpha 2 chain) This gene encodes one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The product of this gene contains several domains similar to von Willebrand Factor type A domains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in this gene are associated with Bethlem myopathy and Ullrich scleroatonic muscular dystrophy. Three transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

LOC124905043 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 21-46111301-C-T is Benign according to our data. Variant chr21-46111301-C-T is described in ClinVar as [Benign]. Clinvar id is 679204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.-27-149C>T		intron_variant		ENST00000300527.9
COL6A2	NM_058174.3	c.-27-149C>T		intron_variant		ENST00000397763.6
LOC124905043	XR_007067910.1	n.731G>A		non_coding_transcript_exon_variant	1/2
COL6A2	NM_058175.3	c.-27-149C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.-27-149C>T		intron_variant		1	NM_001849.4	P1
COL6A2	ENST00000397763.6	c.-27-149C>T		intron_variant		5	NM_058174.3
COL6A2	ENST00000436769.5	c.-27-149C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67094 AN: 152054 Hom.: 16818 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.501 AC: 217999 AN: 435226 Hom.: 56774 AF XY: 0.494 AC XY: 112774 AN XY: 228428

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.364

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.441 AC: 67125 AN: 152172 Hom.: 16835 Cov.: 33 AF XY: 0.448 AC XY: 33306 AN XY: 74374

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.453

Alfa AF: 0.497 Hom.: 3034

Bravo AF: 0.426

Asia WGS AF: 0.400 AC: 1391 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.4
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13050828; hg19: chr21-47531215; COSMIC: COSV56001657; COSMIC: COSV56001657;